tbuckley/cabot-search huggingface dataset:
BT04 Efficient triaging of advice and guidance referrals using teledermatology via the National Health Service Electronic Referral System platform: reporting positive outcomes from the COVID-19 era
Authors: Anthoula Efstathiadou, Kellen Beck-Sander, Wen Ai Woo, Hywel Cooper, Charles Mitchell
Journal: British Journal of Dermatology (2023)

Abstract The provision of teledermatology in National Health Service (NHS) practice has increased markedly over the last decade. The e-Referral System advice and guidance (A&amp;G) is a platform through which teledermatology services can be provided. It was first implemented in our university teaching hospital department in 2016, but extensive use of this system started during the COVID-19 pandemic. Recognizing the practicality of A&amp;G’s ongoing use to triage referrals efficiently, it was made compulsory for all routine referrals to our department in January 2021. We report on A&amp;G triage use on health service outcomes over a 4-year period (June 2019–June 2022). Retrospective analysis of datasets from four timepoints was chosen for comparison: the month of June in 2019, 2020, 2021 and 2022. The main outcomes analysed were total number of A&amp;G requests, number converted to referral, number returned with advice, percentage of discharges at first attendance and referral to treatment (RTT) waiting time performance (defined as percentage of referrals seen in &amp;lt; 18 weeks). The A&amp;G requests increased appreciably over the study period; only 45 requests received in June 2019, increasing to 965 in June 2020 and 1384 in June 2021, and remaining stable (n = 1140) by June 2022. The initial rise was attributable to the COVID-19 pandemic; further increases were due to changing referral pathways. The majority of A&amp;G requests were returned with advice (77.6%, 66.4% and 54.5% in June 2019, 2020 and 2021, respectively), except in June 2022 where 52.2% were converted to referrals. Separate to quantitative analysis, subjective reporting from triaging dermatologists noted improved primary care referral quality (user descriptions, differential diagnoses suggested and treatment options considered), implying educational benefits for referrers, gained from timely and targeted feedback. This was supported by an increasing conversion-to-referral percentage over the period. Triage of referrals allowed the identification of patients requiring advice prior to clinic review, resulting in improved use of clinics. Subsequently, the percentage of referrals discharged after the first clinical encounter decreased from 70% (June 2019) to 29.9% (June 2020), remaining low by June 2022 (37.9%). Concordantly, RTT performance increased from 60.3% in June 2020 to 88.2% 2 years later. The use of A&amp;G to triage all routine referrals has positively impacted on our department’s health service outcomes, noticeably reducing discharges at first attendance and improving RTT performance. We report on these successful outcomes to highlight to other NHS dermatology teams about efficient methods of teledermatology work in an NHS undergoing ever-increasing demands.
Studies on the Response of Patients with Classic Hemophilia to Transfusion with Concentrates of Antihemophilic Factor
Authors: Bruce Bennett, Oscar D. Ratnoff
Journal: Journal of Clinical Investigation (1972)

Antihemophilic factor (AHF, factor VIII) levels were measured by a standard coagulation method and by an immunologic technique before and after infusion of AHF concentrates into patients with classic hemophilia. After infusion of AHF concentrates, the half-life of the AHF procoagulant (i.e., clot-promoting) activity varied from 12 to 14 hr, whereas that of the antigen ranged from 24 to 40 hr. The half-life of the antigen was similar in patients with and without circulating anticoagulants to AHF. The data are compatible with the suggestion that the antigen may be carried on a precursor molecule which the patient with hemophilia produces but cannot convert to the functional clot-promoting agent. Other explanations of the observations are, however, recognized.
Serum 25-hydroxyvitamin D Level is Associated with Arterial Stiffness, Left Ventricle Hypertrophy and Inflammation in Newly Diagnosed Hypertension
Authors: Osman Kuloğlu, Mustafa Gür, Taner Şeker, Gülhan Yüksel Kalkan, Durmuş Yıldıray Şahin, Nermin Yıldız Koyunsever, Hazar Harbalıoğlu, Caner Türkoğlu, Selahattin Akyol, Zafer Elbasan, Armağan Acele, Murat Çaylı
Journal: Journal of the American College of Cardiology (2013)
Avoiding errors and complications related to immediate implant placement in the esthetic area with a mucogingival approach
Authors: Martina Stefanini, Alexandra Rendón, Alessandro Zucchelli, Matteo Sangiorgi, Giovanni Zucchelli
Journal: Periodontology 2000 (2023)

Abstract Immediate implant placement is considered the treatment of choice for single tooth replacement in the esthetic area. However, this treatment is associated with several critical drawbacks related to the inadequate assessment/management of the soft and hard peri‐implant tissues and their subsequent remodeling, resulting in peri‐implant soft‐tissue defects that can lead to impaired esthetic outcomes in time. We describe in detail how the mucogingival approach to immediate implant placement ensures a standard result regardless of the baseline soft‐hard tissue situation. Fully guided implant placement guarantees an adequate three‐dimensional implant placement, the flap design makes it possible to perform bone augmentation with complete visibility of the area being treated, allows soft tissue augmentation with proper fixation of the connective tissue graft, and the placement of an immediate provisional ensures stabilization of the peri‐implant tissues throughout the healing period.
ADNet++: A few-shot learning framework for multi-class medical image volume segmentation with uncertainty-guided feature refinement
Authors: Stine Hansen, Srishti Gautam, Suaiba Amina Salahuddin, Michael Kampffmeyer, Robert Jenssen
Journal: Medical Image Analysis (2023)

A major barrier to applying deep segmentation models in the medical domain is their typical data-hungry nature, requiring experts to collect and label large amounts of data for training. As a reaction, prototypical few-shot segmentation (FSS) models have recently gained traction as data-efficient alternatives. Nevertheless, despite the recent progress of these models, they still have some essential shortcomings that must be addressed. In this work, we focus on three of these shortcomings: (i) the lack of uncertainty estimation, (ii) the lack of a guiding mechanism to help locate edges and encourage spatial consistency in the segmentation maps, and (iii) the models' inability to do one-step multi-class segmentation. Without modifying or requiring a specific backbone architecture, we propose a modified prototype extraction module that facilitates the computation of uncertainty maps in prototypical FSS models, and show that the resulting maps are useful indicators of the model uncertainty. To improve the segmentation around boundaries and to encourage spatial consistency, we propose a novel feature refinement module that leverages structural information in the input space to help guide the segmentation in the feature space. Furthermore, we demonstrate how uncertainty maps can be used to automatically guide this feature refinement. Finally, to avoid ambiguous voxel predictions that occur when images are segmented class-by-class, we propose a procedure to perform one-step multi-class FSS. The efficiency of our proposed methodology is evaluated on two representative datasets for abdominal organ segmentation (CHAOS dataset and BTCV dataset) and one dataset for cardiac segmentation (MS-CMRSeg dataset). The results show that our proposed methodology significantly (one-sided Wilcoxon signed rank test, p<0.05) improves the baseline, increasing the overall dice score with +5.2, +5.1, and +2.8 percentage points for the CHAOS dataset, the BTCV dataset, and the MS-CMRSeg dataset, respectively.
Gigapixel end-to-end training using streaming and attention
Authors: Stephan Dooper, Hans Pinckaers, Witali Aswolinskiy, Konnie Hebeda, Sofia Jarkman, Jeroen van der Laak, Geert Litjens
Journal: Medical Image Analysis (2023)

Current hardware limitations make it impossible to train convolutional neural networks on gigapixel image inputs directly. Recent developments in weakly supervised learning, such as attention-gated multiple instance learning, have shown promising results, but often use multi-stage or patch-wise training strategies risking suboptimal feature extraction, which can negatively impact performance. In this paper, we propose to train a ResNet-34 encoder with an attention-gated classification head in an end-to-end fashion, which we call StreamingCLAM, using a streaming implementation of convolutional layers. This allows us to train end-to-end on 4-gigapixel microscopic images using only slide-level labels. We achieve a mean area under the receiver operating characteristic curve of 0.9757 for metastatic breast cancer detection (CAMELYON16), close to fully supervised approaches using pixel-level annotations. Our model can also detect MYC-gene translocation in histologic slides of diffuse large B-cell lymphoma, achieving a mean area under the ROC curve of 0.8259. Furthermore, we show that our model offers a degree of interpretability through the attention mechanism.
Sarcopenic obesity: emerging mechanisms and therapeutic potential
Authors: Christopher L. Axelrod, Wagner S. Dantas, John P. Kirwan
Journal: Metabolism (2023)

Sarcopenic obesity, or the loss of muscle mass and function associated with excess adiposity, is a largely untreatable medical condition associated with diminished quality of life and increased risk of mortality. To date, it remains somewhat paradoxical and mechanistically undefined as to why a subset of adults with obesity develop muscular decline, an anabolic stimulus generally associated with retention of lean mass. Here, we review evidence surrounding the definition, etiology, and treatment of sarcopenic obesity with an emphasis on emerging regulatory nodes with therapeutic potential. We review the available clinical evidence largely focused on diet, lifestyle, and behavioral interventions to improve quality of life in patients with sarcopenic obesity. Based upon available evidence, relieving consequences of energy burden, such as oxidative stress, myosteatosis, and/or mitochondrial dysfunction, is a promising area for therapeutic development in the treatment and management of sarcopenic obesity.
Interosseous tendon inflammation in the hands of patients with clinically suspect arthralgia: analysis of MRI data from a prospective cohort study
Authors: Bastiaan T van Dijk, Lambertus J Wisse, Hanna W van Steenbergen, Monique Reijnierse, Sarah J H Khidir, Marco C DeRuiter, Annette H M van der Helm-van Mil
Journal: The Lancet Rheumatology (2023)
The Glucocorticoid Toxicity Index-Metabolic Domains, an abridged version of the Glucocorticoid Toxicity Index: post-hoc analysis of data from the ADVOCATE trial
Authors: Naomi J Patel, David R W Jayne, Peter A Merkel, Pirow Bekker, Yuqing Zhang, P Jane McDowell, Joslin Johal, Liam G Heaney, Dedee Murrell, Martha N Stone, Huibin Yue, John H Stone
Journal: The Lancet Rheumatology (2023)
Human papillomavirus integration transforms chromatin to drive oncogenesis
Authors: Mehran Karimzadeh, Christopher Arlidge, Ariana Rostami, Mathieu Lupien, Scott V. Bratman, Michael M. Hoffman
Journal: Genome biology (2023)

Abstract Background Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs predominantly in tumorigenic types of HPV. We hypothesize that changes in chromatin state at the location of integration can result in changes in gene expression that contribute to the tumorigenicity of HPV. Results We find that viral integration events often occur along with changes in chromatin state and expression of genes near the integration site. We investigate whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF binding site, show enriched chromatin accessibility signal. ChIP-seq reveals that the conserved CTCF binding site within the HPV genome binds CTCF in 4 HPV ﻿+ cancer cell lines. Significant changes in CTCF binding pattern and increases in chromatin accessibility occur exclusively within 100 kbp of HPV integration sites. The chromatin changes co-occur with out-sized changes in transcription and alternative splicing of local genes. Analysis of The Cancer Genome Atlas (TCGA) HPV + tumors indicates that HPV integration upregulates genes which have significantly higher essentiality scores compared to randomly selected upregulated genes from the same tumors. Conclusions Our results suggest that introduction of a new CTCF binding site due to HPV integration reorganizes chromatin state and upregulates genes essential for tumor viability in some HPV + tumors. These findings emphasize a newly recognized role of HPV integration in oncogenesis.
Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies
Authors: Danilo Buonsenso, Laura Martino, Rosa Morello, Francesco Mariani, Kelly Fearnley, Piero Valentini
Journal: The Lancet Microbe (2023)

In this Personal View, we discuss current knowledge on SARS-CoV-2 RNA or antigen persistence in children infected with SARS-CoV-2. Based on the evidence that the virus can persist in adults, we have done a literature review and analysed studies that looked for SARS-CoV-2 RNA or antigens in children undergoing autopsy, biopsy, or surgery for either death from COVID-19 or multisystem inflammatory syndrome, or assessments for long COVID-19 or other conditions. Our analysis suggests that in children, independent from disease severity, SARS-CoV-2 can spread systemically and persist for weeks to months. We discuss what is known about the biological effects of viral persistence for other viral infections and highlight new scenarios for clinical, pharmacological, and basic research exploration. Such an approach will improve the understanding and management of post-viral syndromes.
Nicotinamide Adenine Dinucleotide in Aging Biology: Potential Applications and Many Unknowns
Authors: Shalender Bhasin, Douglas Seals, Marie Migaud, Nicolas Musi, Joseph A Baur
Journal: Endocrine Reviews (2023)

Abstract Recent research has unveiled an expansive role of NAD+ in cellular energy generation, redox reactions, and as a substrate or cosubstrate in signaling pathways that regulate health span and aging. This review provides a critical appraisal of the clinical pharmacology and the preclinical and clinical evidence for therapeutic effects of NAD+ precursors for age-related conditions, with a particular focus on cardiometabolic disorders, and discusses gaps in current knowledge. NAD+ levels decrease throughout life; age-related decline in NAD+ bioavailability has been postulated to be a contributor to many age-related diseases. Raising NAD+ levels in model organisms by administration of NAD+ precursors improves glucose and lipid metabolism; attenuates diet-induced weight gain, diabetes, diabetic kidney disease, and hepatic steatosis; reduces endothelial dysfunction; protects heart from ischemic injury; improves left ventricular function in models of heart failure; attenuates cerebrovascular and neurodegenerative disorders; and increases health span. Early human studies show that NAD+ levels can be raised safely in blood and some tissues by oral NAD+ precursors and suggest benefit in preventing nonmelanotic skin cancer, modestly reducing blood pressure and improving lipid profile in older adults with obesity or overweight; preventing kidney injury in at-risk patients; and suppressing inflammation in Parkinson disease and SARS-CoV-2 infection. Clinical pharmacology, metabolism, and therapeutic mechanisms of NAD+ precursors remain incompletely understood. We suggest that these early findings provide the rationale for adequately powered randomized trials to evaluate the efficacy of NAD+ augmentation as a therapeutic strategy to prevent and treat metabolic disorders and age-related conditions.
Thiamine for Renal Protection in Septic Shock (TRPSS): A Randomized, Placebo-controlled, Clinical Trial
Authors: Ari Moskowitz, Katherine M. Berg, Anne V. Grossestreuer, Lakshman Balaji, Xiaowen Liu, Michael N. Cocchi, Maureen Chase, Michelle Ng Gong, Jonathan Gong, Samir M. Parikh, Long Ngo, Noa Berlin, Michael W. Donnino
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Kidney injury is common and associated with worse outcomes in patient with septic shock. Mitochondrial resuscitation with thiamine (vitamin B1) may attenuate septic kidney injury. Objectives: To assess whether thiamine supplementation attenuates kidney injury in septic shock. Methods: The Thiamine for Renal Protection in Septic Shock (TRPSS) trial was a multicenter, randomized, placebo-controlled trial of thiamine vs. placebo in septic shock. The primary outcome was change in serum creatinine between enrollment and 72 hours after enrollment. Measurement and Main Results: Eighty-eight patients were enrolled (42 patients received the intervention and 46 received placebo). There was no significant between-group difference in creatinine at 72-hours (mean difference -0.57, mg/dL, 95% CI -1.18, 0.04, p=0.07). There was no difference in receipt of kidney replacement therapy (14.3% vs. 21.7%, p=0.34), KDIGO-3 acute kidney injury (54.7% vs. 73.9%, p=0.07), or mortality (35.7% vs. 54.3%, p=0.14) between thiamine vs. placebo groups. Patients who received thiamine had more intensive care unit-free days (median 22.5 [IQR 0.0, 25.0] vs. 0.0 [IQR 0.0, 23.0], p<0.01). In the thiamine deficient cohort (27.4% of patients), there was no difference in rates of kidney failure (57.1% thiamine vs. 81.5% placebo) or in-hospital mortality (28.6% vs. 68.8%) between groups. Conclusions: In the TRPSS trial there was no statistically significant difference in the primary outcome of change in creatinine over time. Patients receiving thiamine had more intensive care unit-free days, but no difference in other secondary outcomes. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03550794.
Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism
Authors: Faizan Khan, Doug Coyle, Kednapa Thavorn, Sasha van Katwyk, Tobias Tritschler, Brian Hutton, Grégoire Le Gal, Marc A. Rodger, Dean A. Fergusson
Journal: Annals of Internal Medicine (2023)

Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE).To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE.Markov modeling study.Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events.Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment.Lifetime.Canadian health care public payer.Indefinite anticoagulation with direct oral anticoagulants.Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs).When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person).Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation.The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation.Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE.Canadian Institutes of Health Research.
Deep Learning Assessment of Progression of Emphysema and Fibrotic Interstitial Lung Abnormality
Authors: Samuel Y. Ash, Bina Choi, Andrea Oh, David A. Lynch, Stephen M. Humphries
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Although studies have evaluated emphysema and fibrotic interstitial lung abnormality individually, less is known about their combined progression.
Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares
Authors: Doua F Azzouz, Ze Chen, Peter M Izmirly, Lea Ann Chen, Zhi Li, Chongda Zhang, David Mieles, Kate Trujillo, Adriana Heguy, Alejandro Pironti, Greg G Putzel, Dominik Schwudke, David Fenyo, Jill P Buyon, Alexander V Alekseyenko, Nicolas Gisch, Gregg J Silverman
Journal: Annals of the Rheumatic Diseases (2023)

Objective Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities. Methods In an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed. Results Multivariate analyses documented that, unlike healthy controls, significant temporal community-wide ecological microbiota instability was common in SLE patients, and transient intestinal growth spikes of several pathogenic species were documented. Expansions of only the anaerobic commensal, Ruminococcus (blautia) gnavus (RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares. Conclusions Our findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.